Goldberg L C, Bradley J A, Connolly J, Friend P J, Oliveira D B, Parrott N R, Rodger R S, Taube D, Thick M G
Department of Surgery, Addenbrookes Hospital, Cambridge, United Kingdom.
Transplantation. 1995 May 15;59(9):1285-93.
The perfusion of kidneys with anti-CD45 monoclonal antibodies prior to transplantation offers a means of targeting passenger antigen-presenting cells with the aim of reducing the subsequent incidence of rejection episodes. A safety study was performed in humans of such pretreatment in 40 unsensitized recipients of first cadaveric renal grafts, who were followed for 3 months after transplantation. A 50-ml solution containing 2 mg of each of the rat anti-CD45 mAbs YTH 24.5 and YTH 54.12 was injected into the allograft renal artery ex vivo and just before transplantation while the renal vein was kept clamped. No patients died, but 4 grafts were lost. Two were lost due to primary nonfunction, 1 was lost because of late renal artery thrombosis, and 1 was lost to rejection. There were no cases of renal vein thrombosis and 1 trivial renal artery stenosis, and only 2 patients produced human anti-rat antibodies. Between 63.5% and 100% (median 96.4%) of CD45+ cells in the postperfusion biopsies were coated with anti-CD45 as determined by double-immunolabeling. The number of patients experiencing rejection episodes was inversely associated with this "antibody uptake": 75% of the low uptake group (< 95%) had at least 1 rejection episode, compared with 22% of the high uptake group (> or = 95%) (P = 0.001). The complement components C3 and C5b-9 colocalized with perfused anti-CD45 in 32/33 (97.0%) and 11/33 (33.3%) of the biopsy specimens, respectively. We conclude that: (1) this technique appears free of adverse effects, (2) high antibody uptake within the kidney is associated with a lower incidence of rejection, and (3) the antibodies used fix and activate complement in vivo.
在移植前用抗CD45单克隆抗体灌注肾脏，为靶向过客抗原呈递细胞提供了一种方法，目的是降低随后排斥反应的发生率。对40例初次接受尸体肾移植的未致敏受者进行了这种预处理的人体安全性研究，移植后对他们进行了3个月的随访。在体外和移植前，将含有2mg大鼠抗CD45单克隆抗体YTH 24.5和YTH 54.12的50ml溶液注入同种异体移植肾动脉，同时肾静脉保持夹闭。没有患者死亡，但有4个移植物丢失。2个因原发性无功能丢失，1个因晚期肾动脉血栓形成丢失，1个因排斥反应丢失。没有肾静脉血栓形成的病例，只有1例轻微肾动脉狭窄，只有2例患者产生人抗大鼠抗体。通过双重免疫标记测定，灌注后活检中63.5%至100%（中位数96.4%）的CD45+细胞被抗CD45包被。发生排斥反应的患者数量与这种“抗体摄取”呈负相关：低摄取组（<95%）中75%至少有1次排斥反应，而高摄取组（≥95%）中这一比例为22%（P=0.001）。补体成分C3和C5b-9分别在32/33（97.0%）和11/33（33.3%）的活检标本中与灌注的抗CD45共定位。我们得出结论：（1）该技术似乎没有不良反应；（2）肾脏内高抗体摄取与较低的排斥发生率相关；（3）所用抗体在体内固定并激活补体。
